Pharmaceutical or nutraceutical compositions are designed to release the active ingredient in a manner of reproducible release curves. This shall result in desirable and reliable blood level profiles which shall provide an optimal therapeutic effect. If the blood level concentrations are too low, the active ingredient will not cause a sufficient therapeutic effect. If the blood level concentrations are too high, this may cause toxic effects. In both cases non optimal blood level concentrations of an active ingredient can be dangerous for the patient and shall therefore be avoided. A problem exists in that the ideal ratios assumed for the release of active ingredient during the design of a pharmaceutical or nutraceutical composition can be altered by the general living habits, thoughtlessness or by addictive behaviour of the patients with respect to the use of ethanol or ethanol-containing drinks. In these cases, the pharmaceutical or nutraceutical form which is actually designed for an exclusively aqueous medium is additionally exposed to an ethanol containing medium of greater or lesser strength. Since health authorities like for instance the US Food and Drug Administration (FDA) focus more and more on the ethanol problem, ethanol resistance may be an important registration requirement in the near future.
Since not all patients are aware of the risk of simultaneous taking of a controlled release pharmaceutical or nutraceutical form and ethanol-containing drinks or do not follow or are not able to follow appropriate warnings, advice or recommendations, there is a demand for controlled release pharmaceutical or nutraceutical compositions, especially for extended or sustained release pharmaceutical or nutraceutical compositions, such that their mode of action is affected as little as possible by the presence of ethanol.
Conventional extended or sustained release pharmaceutical or nutraceutical compositions if coated or uncoated are usually not resistant to alcohol at all. Several attempts have been made to provide extended or sustained release pharmaceutical or nutraceutical compositions which are resistant against the influence of ethanol.
US2007/0264346A1 describes multimicroparticulate pharmaceutical forms for oral administration. The oral pharmaceutical or dietic form comprising microparticles of the reservoir type for the modified release of at least one active principle (AP) characterized in that it is resistant to immediate dumping of the dose of AP in the presence of alcohol. The pharmaceutical form may comprise at least one agent D, which is a pharmaceutically acceptable compound whose hydration or solvation rate or capacity is greater in an alcohol-free aqueous medium than in alcoholic medium than in an alcoholic medium. Suitable agent D substances comprise a long list of substances for instance hydroxyalkyl celluloses, guar gums, carragenans, pullulans and mixtures thereof.
US2008/0063725A1 describes prolonged-release multimicroparticulate oral pharmaceutical forms. The oral pharmaceutical form comprising microparticles of the reservoir type with modified release of at least one active principle (AP) which resists immediate AP dose dumping in the presence of alcohol, and which comprises anti-misuse means . The pharmaceutical form may comprise at least one agent D, which is a pharmaceutically acceptable compound whose hydration or solvation rate or capacity is greater in an alcohol-free aqueous medium than in alcoholic medium than in an alcoholic medium. Suitable agent D substances a long list of substances for instance hydroxyalkyl celluloses, guar gums, carragenans, pullulans and mixtures thereof.
US 2012/0328697A1 describes a solid dose form comprising a film coating composition encapsulating a core, wherein: (i) the core comprises an active ingredient comprising at least one of a pharmaceutical, veterinary, or nutraceutical active ingredient; (ii) the film coating composition comprises ethylcellulose and guar gum, wherein the guar gum has an apparent viscosity ≥151.0 cps at a shear rate of 50 s−1 in a 1% aqueous guar gum solution measured rotationally at 20° C. after 1 minute equilibration using a 6 cm acrylic cone)(1° on a cone-plate viscometer wherein the shear is ramped up linearly from 1 to 50 s−1 in 25 steps over 29 seconds; (iii) the dose form provides controlled release of the active ingredient; (iv) the guar gum is present in an amount greater than 5 wt % based on the weight of the guar gum and ethylcellulose; and (v) the dose form is ethanol resistant. In the examples (p. 5, [0063]) theophylline matrix pellets are coated with different ethylcellulose (Aquacoat@ ECD):guar gum blends. The ethylcellulose (Aquacoat@ ECD) is plasticized for 1 day with 25% dibutylsebacate (DBS). Guar gum is dissolved in purified water under stirring for 2 hours. The two liquids are mixed and stirred for 30 min prior to use. The release profiles of the inventive solid dose forms in 0.1 HCl for 2 hours followed by pH buffer pH 7.4 are resistant against the influence of up to 40% ethanol in the 0.1 HCl medium.